Primary infection with varicella-zoster virus (VZV) causes chickenpox, and reactivation of the virus from latency results in zoster. The goals of this project are to identify and determine the function of VZV genes that are expressed during active infection and during latency in the body. VZV genes that are expressed during active infection and regulate viral gene expression in vitro are being studied. Analysis of VZV gene products during acute infection indicate that at least four VZV genes, ORF4, ORF10, ORF61, and ORF62 transactivate the expression of other VZV genes in vitro, and two of these genes (ORF10, ORF62) activate transcription directly. Thus, a limited number of VZV gene products are critical during acute viral infection in regulating VZV replication. Three of these VZV genes (ORF10, ORF61, and ORF62) can complement the function of their herpes simplex virus homologs. Analysis of trigeminal ganglia from human cadavers without active evidence of VZV infection indicates that at least two VZV genes, ORF29 and ORF62, are expressed during viral latency. These genes are expressed exclusively in non- neuronal (satellite) cells. In contrast, other VZV genes, ORF10, ORF28, and ORF61, are not expressed during latency. Therefore, the mechanism of VZV latency in the central nervous system of humans is markedly different from that of the most closely human herpesvirus, herpes simplex virus.